Following our discovery that mutations in Cartilage-Derived Morphogenetic Protein-1 (CDMP-1) cause the clinically severe disorder, Grebe type chondrodyplasia (OMIM number 200700), we have obtained DNA samples from an additional family. However, despite extensive analysis we have not been able to detect a mutation in the coding region of the gene. It is quite possible therefore that a mutation may reside in one of the regulatory regions. With this in mind, we have started to determine the location of functional regulatory elements. Furthermore, as CDMP-1 is the first specific marker expressed in presumptive joint interzones, characterization of cdmp-1 regulatory elements may provide a useful basis for gene targeting approaches to combat degenerative joint disease. Having isolated both mouse and human cdmp-1, we are conducting transient transgenic experiments to determine the location of the cartilage and joint-specific regulatory elements.